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| 2. |
- Almby, Kristina E., et al.
(författare)
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Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
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Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
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| 3. |
- Bengtsson, Johan, et al.
(författare)
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Autonomic modulation networks in schizophrenia : The relationship between heart rate variability and functional and structural connectivity in the brain
- 2020
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 300
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Tidskriftsartikel (refereegranskat)abstract
- Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.
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| 4. |
- Bengtsson, Johan, et al.
(författare)
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Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression
- 2023
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Ingår i: International Journal of Clinical and Health Psychology. - : Elsevier BV. - 1697-2600 .- 2174-0852. ; 23:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression.Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation.Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belong-ing to the active group influenced the choice to guess "active" (odds ratio: 11.7, 95% CI 2.5-53.7). A higher treat-ment intensity of the sham treatment increased the probability to guess "active", but pain did not influence the choice.Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed.
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| 5. |
- Costache, Madalina Elena, et al.
(författare)
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Higher- and lower-order personality traits and cluster subtypes in social anxiety disorder
- 2020
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder.
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| 6. |
- Frick, Andreas, Docent, et al.
(författare)
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Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 261, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD). Methods: Forty-seven SAD patients (mean±SD age 33.9 ± 9.4 years, 24 women) were randomized and commenced 9 weeks’ Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n = 24) or placebo (placebo+CBT, n = 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI-I ≤ 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation. Results: The best model separated treatment responders (n = 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P = 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model. Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available. Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.
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| 7. |
- Guath, Mona, et al.
(författare)
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Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
- 2023
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 436
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Tidskriftsartikel (refereegranskat)abstract
- Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.
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| 8. |
- Hidalgo-Lopez, Esmeralda, et al.
(författare)
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Triple network model of brain connectivity changes related to adverse mood effects in an oral contraceptive placebo-controlled trial
- 2023
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Combined oral contraceptives (COC) are among the most commonly used contraceptive methods worldwide, and mood side effects are the major reason for discontinuation of treatment. We here investigate the directed connectivity patterns associated with the mood side effects of an androgenic COC in a double-blind randomized, placebo-controlled trial in women with a history of affective COC side effects (n = 34). We used spectral dynamic causal modeling on a triple network model consisting of the default mode network (DMN), salience network (SN) and executive control network (ECN). Within this framework, we assessed the treatment-related changes in directed connectivity associated with adverse mood side effects. Overall, during COC use, we found a pattern of enhanced connectivity within the DMN and decreased connectivity within the ECN. The dorsal anterior cingulate cortex (SN) mediates an increased recruitment of the DMN by the ECN during treatment. Mood lability was the most prominent COC-induced symptom and also arose as the side effect most consistently related to connectivity changes. Connections that were related to increased mood lability showed increased connectivity during COC treatment, while connections that were related to decreased mood lability showed decreased connectivity during COC treatment. Among these, the connections with the highest effect size could also predict the participants' treatment group above chance.
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| 9. |
- Hjorth, Olof, et al.
(författare)
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Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder : a randomized clinical trial
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C-11]DASB and [C-11]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.
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| 10. |
- Hjorth, Olof, et al.
(författare)
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Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder : a multitracer positron emission tomography study
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 3970-3979
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.
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